tbuckley/cabot-search huggingface dataset:
PB2300: IMPACT OF INITIAL CHEMOTHERAPY CYCLES AND CLINICAL CHARACTERISTICS ON OUTCOMES FOR HIV-ASSOCIATED DIFFUSE LARGE B CELL LYMPHOMA PATIENTS: THE CENTRAL AND WESTERN CHINA AIDS LYMPHOMA LEAGUE STUDY
Authors: Chaoyu Wang, Yan Wu, Haiyan Min, Yunhong Huang, Yao Liu
Journal: HemaSphere (2023)

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: Little is known about the first line induction chemotherapy cycles for HIV-associated DLBCL as these are less common than HIV-negative lymphoma. Currently, the optimal treatment cycles option remains undefined Aims: Therefore, we performed a multi-center study to analyze the clinical characteristics and outcomes of HIV-associated DLBCL patients in different treatment modes in China Methods: Totally 273 newly diagnosed HIV-associated DLBCL patients at eleven large academic centers from October 2008 to October 2021, were analyzed. Results: In the entire cohort, the median age was 47 years (range, 21-90) at lymphoma diagnosis, and 223 patients were male (81.7%). 194 (71.1%) patients were germinal center B-cell-like lymphoma (GCB) subtype. Most patients (65.2%, 178/273) had elevated LDH, and advanced Ann Arbor stage (78.9% 213/273) at diagnosis. High IPI score (3-5) at diagnosis was found in 65.2% (178/273) of patients. 155 patients (56.8%) had extranodal involvement. The median CD4+ T cell count was 168/μl (range, 2-1067), of whom 174 (63.7%) had a CD4+ T cell count below 200/μl. The median follow‐up of our cohort was 10.1 (0.1-160) months. The overall 2-year OS rates 58.0%. Median OS times in the 0, 1-3, 4-6, and >6 cycles chemotherapy cohort were 7.1 months, 20.0 months, not reached, and not reached, respectively (HR=0.549, 95% CI 0.451-0.667; p<0.001). Cox multivariate analysis showed that age ≥60 (HR=2.207, 95%CI 1.321-3.690; p=0.003), high IPI score (3-5) (HR=2.926, 95% CI 1.716-4.988; p<0.001), B symptoms (HR=1.928, 95%CI 1.192-3.119; p=0.007), elevated LDH (HR=1.696, 95%CI 1.031-2.791; p=0.038) and received less than 4 cycles chemotherapy (HR=0.520, 95%CI 0.424-0.637; p<0.001) were independent risk factor for adverse prognosis based on OS Summary/Conclusion: These results demonstrated that 4-6 cycles chemotherapy were significantly associated with improved outcomes in HIV-associated DLBCL patients. However, >6 cycles chemotherapy did not further improve the survival of patients.Keywords: Survival, Oral, DLBCL, HIV
PB1974: COMPARABLE B2A2/E13A2 AND B3A2/E14A2 REPORTING IN BCR-ABL ASSAY WHEN CALIBRATED BY WHO IS AND BY IVT-RNA COPY NUMBER
Authors: Huilin Wei, Tran Tran, Jessica Saini, Krupa Shridhar, Nick Wang, Gwo-Jen Day
Journal: HemaSphere (2023)

Topic: 8. Chronic myeloid leukemia - Clinical Background: Xpert® BCR-ABL Ultra, automated cartridge-based assay for monitoring BCR-ABL transcript levels, is calibrated by WHO IS to standardize the %reporting for both b2a2/e13a2 BCR-ABL(e13a2) and b3a2/e14a2 BCR-ABL(e14a2) relative to control ABL gene in peripheral blood of patients as a standard management of Chronic Myeloid Leukemia (CML) [1]. Studies have shown differences in patients carrying e13a2 or e14a2 in molecular response to Tyrosine Kinase Inhibitor (TKI) treatment [2-4]. Therefore, it is necessary to understand if there is %reporting differences between two transcripts calibrated by WHO IS[5] and explore the calibration method using breakpoint specific RNA input copy number (CN) for accurate TKI treatment monitoring. Aims: To establish % reporting method calculated with known CN of e13a2, e14a2 and ABL IVT-RNA within a wide CN range and compare % e13a2 and % e14a2 to WHO IS quantification system. Methods: •Three IVT-RNAs, containing e13a2-ABL-BCR, e14a2-ABL-BCR and ABL-BCR, were synthesized as shown in Figure 1.•Serial diluted e13a2 RNA, e14a2 RNA and ABL RNA panels were tested on Xpert BCR-ABL Ultra assay to generate individual standard curve of e13a2 Ct, e14a2 Ct and ABL Ct as a function of CN for % reporting calculation. •Four levels of IVT-RNA panels with same CN of e13a2 and e14a2 were tested for breakpoint specific % reporting comparison. •K562(e14a2), BV173 (e13a2) cell lysates and CML clinical samples carrying e13a2 or e14a2 transcripts were tested to evaluate the %CN reporting compared to WHO IS. Results: •Good linearity demonstrated in Ct - CN input for e13a2, e14a2 and ABL IVT-RNA (Figure2) with comparable efficiency (E) between e13a2 (E=0.992) and e14a2 (E=0.986).•%e13a2 reporting was ~1.50-fold (by WHO IS) and ~1.46-fold (by %CN) higher than %e14a2 by testing IVT-RNA panel (Table1). •Minor differences in %reporting observed between % CN and WHO IS for e13a2 (84.5%~110.8%) vs e14a2 (82.5%~89.5%) from cell lysates (Table2) and e13a2 (92.6%~105.5%) vs e14a2 (88.1%~92.2%) from clinical samples (Table3).Summary/Conclusion: A %CN e13a2/ABL and e14a2/ABL reporting method with known CN of IVT-RNAs has been successfully established in Xpert BCR-ABL Ultra. Both WHO IS and %CN showed very minor differences between e13a2 and e14a2 for % reporting. %CN method demonstrated comparable %reporting to WHO IS in Xpert BCR-ABL Ultra. Keywords: Chronic myeloid leukemia, BCR-ABL, Molecular response
PB2608: THE MANAGEMENT OF IMMUNE THROMBOCYTOPENIA (ITP) IN NORWAY IN THE REAL LIFE – ANALYSIS OF THE NOR-ITP REGISTRY
Authors: Ekaterina Ilicheva, Eirik Tjønnfjord, Riccardo Tomasello, Heidi Pettersen, Hoa Tran, Galina Tsykonova, Lamya Garabet, Geir Tjønnfjord, Waleed Ghanima
Journal: HemaSphere (2023)

Topic: 32. Platelet disorders Background: Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by immune-mediated platelet destruction associated with suboptimal platelet production. The management of ITP is rapidly evolving. Accordingly, it is important to know how available therapies are used in real life as well as the effectiveness and safety of these therapies. Aims: This study aimed first to describe the Norwegian ITP registry and second to determine the patterns and outcomes of ITP management in adults with ITP in Norway. Methods: We enrolled 255 adult patients from the Norwegian ITP Registry. The Norwegian ITP (NOR-ITP) Registry is a multicenter, dynamic quality control registry for children and adult ITP in Norway. Adult ITP patients are included from four participating centers in Norway. All registered patients have provided written informed consent. Results: Median age of 255 patients was 53 years, of these, 61% were females. Of these, 7% had secondary ITP at diagnosis. Almost half (44%) of the patients had bleeding at diagnosis. Skin and mucosal bleeding, together with epistaxis, were the three most frequent types of bleeding. Autoimmune disease and diabetes were the most frequent comorbidities at diagnosis. Of all patients, 15% never received treatment, whereas 205 of all treated patients (94%) received corticosteroids as first-line treatment. Eighty patients (37%) received corticosteroids as the only treatment. The median duration of treatment with corticosteroids was 4 months after 2020 compared to 6 months before 2020. The use of Intravenous immunoglobulin (IVIG) and platelet transfusion was relatively high (40% and 30% percent). The two most common second-line therapies were rituximab and TPO-RA (thrombopoietin-receptor agonist), followed by splenectomy, which was performed in 19% of the patients. Remission rate in patients who received corticosteroids as the only treatment was between 80% and 90%, depending on the type of corticosteroids. However, the remission rate in patients who received rituximab as the second-line treatment was 67% at median observation time of 46 months. Summary/Conclusion: Most of our findings are in line with data from other similar studies. A substantial proportion of patients received corticosteroids only and achieved remission. However, the median duration of treatment with corticosteroids was longer than what is recommended by the recent guidelines published in 2019. The high use of IVIG and platelet transfusion in ITP is definitely a practice that needs to be challenged. Keywords: Immune thrombocytopenia (ITP)
P1262: GILTERITINIB MAINTENANCE AFTER ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR RELAPSED/REFRACTORY ACUTE MYELOID LEUKEMIA WITH FLT3–INTERNAL TANDEM DUPLICATION MUTATION
Authors: Chen Liang, Yi He, Aiming Pang, Donglin Yang, Rongli Zhang, Weihua Zhai, Xiaojin Wu, Sizhou Feng, Mingzhe Han, Erlie Jiang
Journal: HemaSphere (2023)

Topic: 22. Stem cell transplantation - Clinical Background: Patients with relapsed or refractory (r/r) acute myeloid leukemia (AML) with FLT3-Internal Tandem Duplication (ITD) mutation have a poor prognosis and high risk of relapse, even after allogeneic hematopoietic stem cell transplantation (HSCT). Prevention of disease relapse remains a challenge. Aims: To investigate the efficacy and tolerability of gilteritinib maintenance therapy post-transplantation in r/r AML patients with FLT3-ITD mutation. Methods: We compared different post-transplant maintenance therapies in 94 FLT3-ITD mutated r/r AML patients. A retrospective matched-pair analysis was performed. Patients were divided into two groups based on the maintenance therapy used, with 44 patients in the gilteritinib group and 50 patients in the control group (sorafenib/demethylating agents, or other targeted therapeutics were used as maintenance therapy). The therapeutic process and clinical outcome were retrospectively analyzed. Results: A total of 46.8% (44/94) of the patients had primary refractory disease and 42.6% (40/94) had recurrent AML. The remaining 10 patients were transplanted in CR1 but were detected with persistent MRD positivity during chemotherapy. Sixty-two patients (66.0%) were found to be MRD positive at the time of transplantation and 28 patients (29.8%) were transplanted with active disease. Gilteritinib maintenance therapy was associated with an improvement in overall survival (OS) (88.1% (95% CI 76.9-99.3%) vs. 65.1% (95% CI 51.6-78.6%), P=0.003) and relapse free survival (RFS) (75.7% (95% CI 62.6-88.8%) vs. 52.0% (95% CI 38.1-65.9%), P=0.006) at 2-years, when compared with the control group. Relapse remained the main reason of treatment failure with 2-year incidence of 25.4% (95%CI 12.7-40.2%) and 58.5% (95%CI 42.4-71.5%) for the gilteritinib group and the control group, respectively (P=0.004). Cumulative incidence of non-relapse mortality (NRM) at 2-years was similar (P= 0.744). In multivariate Cox regression analysis, gilteritinib maintenance therapy was the only factor associated with improved OS (HR=0.240, 95% CI 0.090–0.641, P=0.004) and RFS (HR=0.430, 95% CI 0.215–0.858, P=0.017). Cumulative incidence of day 100 aGVHD (P=0.083) and 2-year cGVHD (P=0.136) was comparable between the gilteritinib group and the control group. Summary/Conclusion: Our results indicated that gilteritinib maintenance therapy reduced the risk of relapse after HSCT for patients with FLT3-ITD mutated r/r AML. Compared with other maintenance therapies, gilteritinib treatment showed a similar incidence of NRM and GVHD, leading to an improvement in OS and RFS. Keywords: flt3 inhibitor, Maintenance, Allogeneic hematopoietic stem cell transplant, Acute myeloid leukemia
Impact of Coronary Artery Disease in Women With Newly Diagnosed Heart Failure and Reduced Ejection Fraction
Authors: Roni Ranghoej Nielsen, Nanna Anker, Nina Stødkilde-Jørgensen, Pernille Gro Thrane, Malene Kærslund Hansen, Kasper Pryds, Martin Bødtker Mortensen, Kevin Kris Warnakula Olesen, Michael Maeng
Journal: JACC Heart Failure (2023)
PB1857: VENETOCLAX, AZACITIDINE, COMBINED WITH LOW-DOSE CYTARABINE IN OLDERLY OR UNFIT PATIENTS WITH NEWLY DIAGNOSED ACUTE MYELOID LEUKEMIA
Authors: Xiao Han, Qin Wen, Kai Wan, Xue Liu, Hongju Yan, Xu Tan, Yang Bao, Cheng Zhang, XI Zhang
Journal: HemaSphere (2023)

Topic: 4. Acute myeloid leukemia - Clinical Background: Older or unfit patients with acute myeloid leukemia (AML) have a dismal prognosis. The combination of venetoclax with azacitidine had promising efficacy, and well tolerated in elderly patients with AML, but the minimal residual disease (MRD) negative rate is only 30-40%.In most cases measurable residual disease (MRD) positivity predicts hematologic relapse potentially allowing early therapeutic intervention. Aims: To explore the efficacy and safety of Ven+AZA+LDAC induction therapy for older or unfit adult AML. Methods: This is a prospective, one-arm, multicenter, open clinical trial, Adults age ≥18 years with newly diagnosed AML ineligible for intensive chemotherapy were enrolled.Patients received induction treatment with venetoclax 100mg d1 200mg d2 400mg d3-28, azacytidine 75mg/m2 d1-7, cytarabine10mg/m2 q12h d1-7. The primary observation was the remission rate(CR/CRi) and the negative rate of MRD. Secondary end points included total effective rate (ORR), safety and tolerability, including dose limiting toxicity (DLT) and adverse events (AE). Results: the baseline characteristics of 20 older or unfit patients who can evaluate the efficacy are shown in Table 1. After the first course of Ven+AZA+LDAC treatment, 12 patients (60%) reached CR with negative MRD, 5 patients (25%) reached CR with positive MRD, 2 patients (10%) had partial remission (PR), 1 patient (5%) had no remission (NR), and the ORR was 95%. Subgroup analysis showed that of 11 elderly patients, 8 (72.7%) had CR with MRD negative, 2 (18.2%) had CR with MRD positive, and 1 (9.1%) had partial remission (PR); Of the 9 patients initially diagnosed with unfit, 7 (77.8%) reached CR, of which 4 (57.1%) were negative for MRD, 1 (11.1%) had partial remission (PR), and 1 (11.1%) had no remission (NR). Safety: All the 11 elderly patients had febrile neutropenia, which controlled after therapy, without severe infection and bleeding complications. 9 patients with unfit had severe complications such as severe infection, respiratory failure, or intracranial hemorrhage before treatment, but no treatment-related deaths occurred during the induction period. Related adverse reaction are shown in Figure 1. Summary/Conclusion: In conclusion, in newly diagnosed patients who were ineligible for intensive chemotherapy, the incidence of remission was higher among patients who received Ven+AZA+LDAC, and some patients can quickly obtain negative MRD. Infection, chemotherapy-related mortality, and the tolerability were acceptable. However, it is necessary to further expand the sample size and extend the follow-up time to assess the long-term survival rate.Keywords: Aging, Venetoclax, AML
Lactate acidosis and simultaneous recruitment of TGF-β leads to alter plasticity of hypoxic cancer cells in tumor microenvironment
Authors: Saumya Rastogi, Shashank Shekher Mishra, Mandeep Kumar Arora, Gaurav Kaithwas, Sugato Banerjee, Velayutham Ravichandiran, Subhadeep Roy, Lakhveer Singh
Journal: Pharmacology & Therapeutics (2023)
PB2653: SYNTHESIS OF MAGNETIC NANOPARTICLES SUITABLE FOR PURIFICATION FACTOR VIII
Authors: Nataliya Shurko, Taras Danysh
Journal: HemaSphere (2023)

Topic: 33. Bleeding disorders (congenital and acquired) Background: Magnetic nanoparticles (MNPs) are well-established nanomaterials that offer controlled size, ability to be manipulated externally, and enhancement of contrast in magnetic resonance imaging. The use of MNPs offers major advantages due to their unique size and physicochemical properties. Much attention has been paid to the synthesis of different kinds of MNPs because they widespread applications in biotechnology, biomedical, material science, engineering, including protein purification, drug delivery, and medical imaging. Iron oxide nanoparticles (magnetite (Fe3O4) or its oxidized form maghemite (γ-Fe2O3)) are by far the most commonly employed nanoparticles for biomedical applications. The iron oxide MNPs can be synthesized by adopting versatile synthetic approaches include solution precipitation, thermal decomposition, co-precipitation, micelle formation, hydrothermal and laser pyrolysis techniques, biological synthesis etc. Aims: synthesis iron oxide MNPs and investigate the possibility their use in the technology of purification of blood coagulation factor VIII (FVIII). Methods: in the work, nanoparticles with different core sizes (from 80 to 500 nm) were used. The obtained MNPs are functionalized with carboxyl and amino groups. For fractionation of MNPs a tripod with a constant field neodymium magnet (0.24 T; Sphere Sim, Lviv) was used. Results: By the co-precipitation method were synthesized 6 classes of MNPs with different core sizes and functional groups: MNP-COOH-500 nm; MNP-PEG-COOH-300 nm; MNP-NH2-250 nm; MNP-NH2-130 nm; MNP-NH2-80 nm; MNP-OH-250 nm. In the production process, two approaches were used: without and with the use of stabilizers. By means of magnetic separation using neodymium permanent magnets, MNP fractionation was carried out into the following fractions: < 50 nm, 50-100 nm, > 100 nm. A study of the influence of MNPs on FVIII activity was conducted. The initial concentration of FVIII was 1.0 IU/ml, the concentration of MNPs – 50 μg/ml. The activity of FVIII in the solution was reduced by 50 % after the action of the magnet using the following MNPs: MNP-PEG-COOH-300; MNP -NH2-250; MNP-NH2-80 and MNP-OH-250. Summary/Conclusion: Experimental studies have confirmed that the synthesized MNPs may be suitable for further analysis FVIII, for effective use and modernization of technological schemes for the selection of this protein from plasma of blood by the magnetic method affinity chromatography (bioseparation). Keywords: Factor VIII
P1620: A CROSS-NATIONAL SURVEY OF PEOPLE LIVING WITH HEMOPHILIA: REPORTED PAIN, IMPACT ON PHYSICAL ACTIVITY AND OPPORTUNITY ON USING DIGITAL TOOLS FOR MONITORING HAEMOPHILIA
Authors: Atanas Banchev, Angelika Bátorová, Ana Boban, Melen Brinza, Barbara Faganel Kotnik, Letitia Pintilie-Ancuta, Ester Zapotocka
Journal: HemaSphere (2023)

Topic: 33. Bleeding disorders (congenital and acquired) Background: The Liberate Life® project aims to provide support and information to patients with haemophilia (PwH), which may help to limit the impact of haemophilia on their quality of life (QoL). In the first wave of the Liberate Life survey (performed from December 2020–May 2021), pain, bleeding and their impact on QoL were identified as key issues for PwH (Banchev A et al. Patient Preference and Adherence 2021:15;871–883). Given that the strategies used by PwH to manage pain are poorly understood, a deeper understanding of these issues for PwH and their caregivers was sought. The use of digital tools for the self-management of haemophilia was also investigated to help identify how patient-oriented information and education can be improved to assist PwH in managing their condition. Aims: To gain insight about haemophilia-related joint pain (HRJP), pain management, and the use of digital tools for PwH in Central and Eastern Europe. Methods: The second wave of the Liberate Life survey was sponsored by Swedish Orphan Biovitrum (Bratislava, Slovakia) and conducted online using the TypeForm™ platform in Bulgaria, Croatia, the Czech Republic, Hungary, Romania, Slovakia and Slovenia. Data collection was performed using Surveysparrow® from 14 February–01 March 2022. Adults and children with haemophilia A or B of any severity and/or their caregivers were eligible to participate in this survey. The survey results are reported using descriptive statistics. Results: Survey respondents (N=274) were either PwH (n=170) or their caregivers (n=104). Overall, 24% of PwH respondents reported 1 painful joint and 28% reported 2 painful joints in the past year, while 25% of PwH caregivers reported 1 painful joint and 18% reported 2 painful joints in the past year. Of survey respondents, 52% of PwH and 33% of caregivers of PwH reported HRJP at least once a month. HRJP was highlighted as a limiting factor in physical and social activity. The most common action taken to address HRJP was a reduction in physical activity (62%), followed by taking pain medication (29%). In total, 40% of respondents were aware of Liberate Life, with 8% using this resource regularly. Other digital tools used regularly by survey respondents include florio® HAEMO (15%) and myWAPPS (3%). Summary/Conclusion: HRJP represents a prevalent reported issue and opportunity to improve disease management and QoL for PwH. The awareness and use of digital tools, such as Liberate Life and florio® HAEMO, has increased since the first wave of the Liberate Life survey performed in 2021. Keywords: Hemophilia A, Hemophilia B, Quality of life
Exposure to Polystyrene Nanoplastics Led to Learning and Memory Deficits in Zebrafish by Inducing Oxidative Damage and Aggravating Brain Aging
Authors: Weishang Zhou, Difei Tong, Dandan Tian, Yingying Yu, Lin Huang, Weixia Zhang, Yihan Yu, Lingzheng Lu, Xunyi Zhang, Wangqi Pan, Jiawei Shen, Wei Shi, Guangxu Liu
Journal: Advanced Healthcare Materials (2023)

Nanoplastics (NPs) may pass through the blood-brain barrier, giving rise to serious concerns about their potential toxicity to the brain. In this study, the effects of NPs exposure on learning and memory, the primary cognitive functions of the brain, are assessed in zebrafish with classic T-maze exploration tasks. Additionally, to reveal potential affecting mechanisms, the impacts of NPs exposure on brain aging, oxidative damage, energy provision, and the cell cycle are evaluated. The results demonstrate that NP-exposed zebrafish takes significantly longer for their first entry and spends markedly less time in the reward zone in the T-maze task, indicating the occurrence of learning and memory deficits. Moreover, higher levels of aging markers (β-galactosidase and lipofuscin) are detected in the brains of NP-exposed fish. Along with the accumulation of reactive free radicals, NP-exposed zebrafish suffer significant levels of brain oxidative damage. Furthermore, lower levels of Adenosine triphosphate (ATP) and cyclin-dependent kinase 2 and higher levels of p53 are observed in the brains of NP-exposed zebrafish, suggesting that NPs exposure also results in a shortage of energy supply and an arrestment of the cell cycle. These findings suggest that NPs exposure may pose a severe threat to brain health, which deserves closer attention.
Ecological tips to reduce waste during acetic acid dye application for Barrett’s esophagus evaluation: a small syringe in the accessory channel is enough!
Authors: Elena De Cristofaro, Raphaelle Grau, Pierre Lafeuille, Clara Yzet, Florian Rostain, Jérôme Rivory, Mathieu Pioche
Journal: Endoscopy (2023)

It is common knowledge that endoscopic procedures have a non-negligible ecological impact [1], and every effort to address this impact can contribute to reduction in the associated waste and ecological footprint of the procedure [2].
Endoscopic ultrasound-guided super-selective partial splenic embolization: New embolic material and multiple safety precautions
Authors: Wei Wu, Qi Wang, Yubei Gu, Yunwei Sun, Dong Wang, Duowu Zou, Zhiyuan Wu
Journal: Endoscopy (2023)

Partial splenic embolization (PSE) has proven useful in the management of two of the common sequelae of portal hypertension: bleeding varices and hypersplenism [1]. A combination of PSE and endoscopic therapy tends to further decrease the risk of variceal bleeding [2]. The authors have focused on enhancing the safety of endoscopic-ultrasound (EUS)-guided PSE [3] through super-selection and controlled embolization of the lower pole branch of the splenic artery and its supply area, utilization of a thinner needle, and double validation of the punctured artery. The delivery process of embolic material has been simplified as well ([Video 1]).